CircAURKA: A Novel Circular RNA Associated with Colorectal Cancer Prognosis and Progression
A recent study has identified a circular RNA molecule named circAURKA, which is highly expressed in colorectal cancer (CRC) tissues and affects the prognosis of patients. This circular RNA is derived from the AURKA gene, a key regulator of cell division. circAURKA expression was found to be significantly higher in CRC cells and tissues compared to normal colonic epithelial cells, suggesting its potential as a diagnostic marker.
CircAURKA exhibits a distinct circular structure, formed through back-splicing of the AURKA gene’s exons 6-9. This circular structure provides circAURKA with enhanced stability compared to its linear counterpart, as it is resistant to degradation by exonucleases and exhibits a longer half-life. circAURKA is localized primarily in the cytoplasm, and its expression correlates with the stage of CRC and the presence of lymph node metastasis.
Functional studies demonstrate that circAURKA plays a crucial role in promoting CRC progression. Interference with circAURKA expression significantly reduced cell proliferation, migration, and invasion in CRC cell lines, while overexpression of circAURKA exhibited the opposite effects. Furthermore, in vivo studies using nude mouse models confirmed that circAURKA promotes tumor growth and metastasis.
The molecular mechanisms underlying circAURKA’s oncogenic activity were unraveled through transcriptomic analysis. The study revealed that circAURKA interacts with the proteins ACLY and CTNNB1, key components of the Wnt pathway. CircAURKA promotes the association of ACLY with CTNNB1, leading to the stabilization of CTNNB1 protein and activation of Wnt signaling. This activation, in turn, drives cell proliferation, migration, and invasion, ultimately contributing to CRC progression.
Further investigation revealed that circAURKA is subject to N6-methyladenosine (m6A) methylation. This modification enhances circAURKA stability and further promotes its oncogenic activity. Mutation of the m6A sites on circAURKA resulted in reduced stability and a decrease in its ability to promote CRC cell migration and invasion.
This study provides significant insights into the role of circAURKA in CRC progression. Its high expression, stable circular structure, and ability to promote Wnt signaling highlight its potential as a therapeutic target, while its m6A modification provides another avenue for therapeutic intervention. Future research will focus on further understanding the intricate mechanisms of circAURKA and its therapeutic potential in CRC treatment.